Acute adenoviral infection has been associated with severe lung disease. Chronic sequelae may also result from adenoviral infection, such as hyperlucent lung syndrome and chronic obstructive lung disease. Various cytokines, especially tumor necrosis factor (TNF) appear to be necessary for the development of many acute and chronic lung diseases. Since the early genes of adenovirus are expressed during latency and during acute infection, the regulation of cytokine production by -these genes may be important in the pathogenesis of both acute and chronic sequelae of adenoviral infection. The purpose of this proposal is to advance our understanding of the mechanisms by which adenovirus regulates the TNF gene. We will first assess whether adenovirus early genes can upregulate the TNF gene. Next, we will examine the mechanism of this regulation both from the standpoint of the viral genome and from the standpoint of the TNF gene itself. Finally, we will assess whether or not these same mechanisms are important in the regulation of TNF by whole adenovirus following acute infection of human inflammatory cell lines in vitro.